Study to Assess the Efficacy and Safety of Treatment With FOLFIRI-aflibercept Compared to Initial Treatment With FOLFIRI-aflibercept (for 6 Cycles) Followed by Maintenance With 5FU-aflibercept, in an Elderly Population With mCRC After Failure of an Oxaliplatin-based Regimen

NCT ID: NCT03279289

Last Updated: 2023-04-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-25
• Study Completion Date: 2023-02-09

Brief Summary

The purpose of this study is to assess the efficacy and safety of treatment with FOLFIRI-aflibercept compared to initial treatment with FOLFIRI-aflibercept (for 6 cycles) followed by maintenance with 5FU-aflibercept, in an elderly population with metastatic colorectal cancer (mCRC) after failure of an oxaliplatin-based regimen

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A

INDUCTION PHASE: 6 cycles of FOLFIRI + aflibercept MAINTENANCE PHASE: 5FU/LV + aflibercept

Group Type: EXPERIMENTAL

Aflibercept

Intervention Type: DRUG

4 mg/kg administered intravenous infusion on day 1

Irinotecan

Intervention Type: DRUG

180 mg/m2 intravenous infusion

folinic acid (dl racemic)

Intervention Type: DRUG

400 mg/m2 intravenous infusion

5Fluorouracil

Intervention Type: DRUG

400 mg/m2 intravenous bolus

5-FU

Intervention Type: DRUG

2400 mg/m2 continuous intravenous infusion over 46 hours

Group B

FOLFIRI + aflibercept

Group Type: ACTIVE_COMPARATOR

Aflibercept

Intervention Type: DRUG

4 mg/kg administered intravenous infusion on day 1

Irinotecan

Intervention Type: DRUG

180 mg/m2 intravenous infusion

folinic acid (dl racemic)

Intervention Type: DRUG

400 mg/m2 intravenous infusion

5Fluorouracil

Intervention Type: DRUG

400 mg/m2 intravenous bolus

5-FU

Intervention Type: DRUG

2400 mg/m2 continuous intravenous infusion over 46 hours

Interventions

Aflibercept

4 mg/kg administered intravenous infusion on day 1

Intervention Type: DRUG

Irinotecan

180 mg/m2 intravenous infusion

Intervention Type: DRUG

folinic acid (dl racemic)

400 mg/m2 intravenous infusion

Intervention Type: DRUG

5Fluorouracil

400 mg/m2 intravenous bolus

Intervention Type: DRUG

5-FU

2400 mg/m2 continuous intravenous infusion over 46 hours

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Signed and dated informed consent, and willing and able to comply with protocol requirements,

2. Histologically proven adenocarcinoma of the colon and/or rectum,

3. Existence of at least one measurable unidimensional lesion using CT or MRI based on the RECIST criteria, version 1.1

4. Patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed after a first line oxaliplatin-containing regimen for metastatic disease.

5. Age ≥70 years

6. World Health Organization (WHO) Performance status (PS) 0-2,

7. Hematological status: neutrophils (ANC) ≥1.5x109 /L; platelets ≥100x109 /L; haemoglobin ≥9 g/dL

8. Adequate renal function: Creatinine clearance ≥50 mL/min as calculated using the Cockcroft-Gault equation.

9. Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkaline phosphatase (ALP) <5xULN

10. Proteinuria <2+ (dipstick urinalysis) or ≤1g/24hour.

11. Regular follow-up feasible.

12. Male patients with a partner of childbearing potential must agree to use contraception in addition to having their partner use another contraceptive method during the trial.

Exclusion Criteria

1. Uncontrolled hypercalcemia,

2. Pre-existing permanent neuropathy (NCI grade >2)

3. Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy,

4. Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),

5. Treatment with any other investigational medicinal product within 28 days prior to study entry.

6. Other serious and uncontrolled non-malignant disease,

7. History or evidence upon physical examination of CNS metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy),

8. Patients classified as fragile or delicate according to the following criteria:

1. Dependence in one or more activities of daily living according to the Katz Index of Independence in Activities of Daily Living (ADL) scale

2. Three or more comorbidities when assessing the presence of the following processes: congestive heart failure; heart valve disease; coronary artery disease; chronic (obstructive or restrictive) pulmonary disease; cerebrovascular disease; peripheral neuropathy, chronic kidney failure; hypertension; diabetes; concomitant cancers; collagen vascular disease; chronic liver disease; and disabling arthritis

3. Presence of geriatric syndromes: moderate-severe dementia; delirium in stressful situations (urinary or respiratory tract infection, angina or drugs); moderate-severe depression that interferes with the patient's usual activity; frequent falls (three or more per month); inattentiveness (who could help you in the event of an emergency?); urinary incontinence in the absence of stress, infection, diuretics or prostatic hyperplasia; faecal incontinence in the absence of diarrhoea or laxatives; osteoporotic fractures of large bones or vertebral compression fractures

9. Known Gilbert's syndrome

10. Intolerance to atropine sulfate or loperamide

11. Known dihydropyrimidine dehydrogenase deficiency

12. Treatment with CYP3A4 inducers unless discontinued > 7 days prior to inclusion

13. Any of the following in 3 months prior to inclusion: grade 3-4 gastrointestinal bleeding (unless due to resected tumor), treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulitis.

14. Other concomitant or previous malignancy, except: i/ adequately treated insitu carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years,

15. Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days

16. Patients with known allergy to any excipient to study drugs,

17. History of myocardial infarction and/or stroke within 6 months prior to inclusion, NYHA class III and IV congestive heart failure

18. Bowel obstruction.

19. Less than 28 days elapsed from prior radiotherapy

20. Patients with pernicious anemia or other megaloblastic anemias due to vitamin B12 deficiency

21. Patients with severe infections

• Minimum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pilar García Alfonso

Role: STUDY_CHAIR

Hospital Universitario Gregorio Marañón

Javier Sastre Valera

Role: STUDY_CHAIR

Hospital Universitario Clínico San Carlos

Locations

Spanish Cooperative Group for Digestive Tumour Therapy (TTD)

Madrid, , Spain

Countries

Spain

Other Identifiers

TTD-16-03

Identifier Type: -

Identifier Source: org_study_id